@article{fix_novell_yun_dayton_arena_2017, title={An evaluation of the sonoporation potential of low-boiling point phase-change ultrasound contrast agents in vitro}, volume={5}, ISSN={["2050-5736"]}, DOI={10.1186/s40349-017-0085-z}, abstractNote={Phase-change ultrasound contrast agents (PCCAs) offer a solution to the inherent limitations associated with using microbubbles for sonoporation; they are characterized by prolonged circulation lifetimes, and their nanometer-scale sizes may allow for passive accumulation in solid tumors. As a first step towards the goal of extravascular cell permeabilization, we aim to characterize the sonoporation potential of a low-boiling point formulation of PCCAs in vitro.Parameters to induce acoustic droplet vaporization and subsequent microbubble cavitation were optimized in vitro using high-speed optical microscopy. Sonoporation of pancreatic cancer cells in suspension was then characterized at a range of pressures (125-600 kPa) and pulse lengths (5-50 cycles) using propidium iodide as an indicator molecule.We achieved sonoporation efficiencies ranging from 8 ± 1% to 36 ± 4% (percent of viable cells), as evidenced by flow cytometry. Increasing sonoporation efficiency trended with increasing pulse length and peak negative pressure.We conclude that PCCAs can be used to induce the sonoporation of cells in vitro, and our results warrant further investigation into the use of PCCAs as extravascular sonoporation agents in vivo.}, journal={JOURNAL OF THERAPEUTIC ULTRASOUND}, author={Fix, Samantha M. and Novell, Anthony and Yun, Yeoheung and Dayton, Paul A. and Arena, Christopher B.}, year={2017}, month={Jan}, pages={1–11} }
 @article{novell_arena_oralkan_dayton_2016, title={Wideband acoustic activation and detection of droplet vaporization events using a capacitive micromachined ultrasonic transducer}, volume={139}, ISSN={["1520-8524"]}, DOI={10.1121/1.4953580}, abstractNote={An ongoing challenge exists in understanding and optimizing the acoustic droplet vaporization (ADV) process to enhance contrast agent effectiveness for biomedical applications. Acoustic signatures from vaporization events can be identified and differentiated from microbubble or tissue signals based on their frequency content. The present study exploited the wide bandwidth of a 128-element capacitive micromachined ultrasonic transducer (CMUT) array for activation (8 MHz) and real-time imaging (1 MHz) of ADV events from droplets circulating in a tube. Compared to a commercial piezoelectric probe, the CMUT array provides a substantial increase of the contrast-to-noise ratio.}, number={6}, journal={JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA}, author={Novell, Anthony and Arena, Christopher B. and Oralkan, Omer and Dayton, Paul A.}, year={2016}, month={Jun}, pages={3193–3198} }
 @article{arena_novell_sheeran_puett_moyer_dayton_2015, title={Dual-Frequency Acoustic Droplet Vaporization Detection for Medical Imaging}, volume={62}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2014.006883}, abstractNote={Liquid-filled perfluorocarbon droplets emit a unique acoustic signature when vaporized into gas-filled microbubbles using ultrasound. Here, we conducted a pilot study in a tissue-mimicking flow phantom to explore the spatial aspects of droplet vaporization and investigate the effects of applied pressure and droplet concentration on image contrast and axial and lateral resolution. Control microbubble contrast agents were used for comparison. A confocal dual-frequency transducer was used to transmit at 8 MHz and passively receive at 1 MHz. Droplet signals were of significantly higher energy than microbubble signals. This resulted in improved signal separation and high contrast-to-tissue ratios (CTR). Specifically, with a peak negative pressure (PNP) of 450 kPa applied at the focus, the CTR of B-mode images was 18.3 dB for droplets and -0.4 for microbubbles. The lateral resolution was dictated by the size of the droplet activation area, with lower pressures resulting in smaller activation areas and improved lateral resolution (0.67 mm at 450 kPa). The axial resolution in droplet images was dictated by the size of the initial droplet and was independent of the properties of the transmit pulse (3.86 mm at 450 kPa). In post-processing, time-domain averaging (TDA) improved droplet and microbubble signal separation at high pressures (640 kPa and 700 kPa). Taken together, these results indicate that it is possible to generate high-sensitivity, high-contrast images of vaporization events. In the future, this has the potential to be applied in combination with dropletmediated therapy to track treatment outcomes or as a standalone diagnostic system to monitor the physical properties of the surrounding environment.}, number={9}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Arena, Christopher B. and Novell, Anthony and Sheeran, Paul S. and Puett, Connor and Moyer, Linsey C. and Dayton, Paul A.}, year={2015}, month={Sep}, pages={1623–1633} }
 @article{novell_legros_gregoire_dayton_bouakaz_2014, title={Evaluation of bias voltage modulation sequence for nonlinear contrast agent imaging using a capacitive micromachined ultrasonic transducer array}, volume={59}, ISSN={["1361-6560"]}, DOI={10.1088/0031-9155/59/17/4879}, abstractNote={Many clinical diagnoses have now been improved thanks to the development of new techniques dedicated to contrast agent nonlinear imaging. Over the past few years, Capacitive Micromachined Ultrasonic Transducers (cMUTs) have emerged as a promising alternative to traditional piezoelectric transducers. One notable advantage of cMUTs is their wide frequency bandwidth. However, their use in nonlinear imaging approaches such as those used to detect contrast agents have been challenging due their intrinsic nonlinear character. We propose a new contrast imaging sequence, called bias voltage modulation (BVM), specifically developed for cMUTs to suppress their inherent nonlinear behavior. Theoretical and experimental results show that a complete cancellation of the nonlinear signal from the source can be reached when the BVM sequence is implemented. In-vitro validation of the sequence is performed using a cMUT probe connected to an open scanner and a flow phantom setup containing SonoVue microbubbles. Compared to the standard amplitude modulation imaging mode, a 6 dB increase of contrast-to-tissue ratio was achieved when the BVM sequence is applied. These results reveal that the problem of cMUT nonlinearity can be addressed, thus expanding the potential of this new transducer technology for nonlinear contrast agent detection and imaging.}, number={17}, journal={PHYSICS IN MEDICINE AND BIOLOGY}, author={Novell, Anthony and Legros, Mathieu and Gregoire, Jean-Marc and Dayton, Paul A. and Bouakaz, Ayache}, year={2014}, month={Sep}, pages={4879–4896} }
 @article{novell_sennoga_escoffre_chaline_bouakaz_2014, title={Evaluation of chirp reversal power modulation sequence for contrast agent imaging}, volume={59}, number={17}, journal={Physics in Medicine & Biology}, author={Novell, A. and Sennoga, C. A. and Escoffre, J. M. and Chaline, J. and Bouakaz, A.}, year={2014}, pages={5101–5117} }
 @article{arena_novell_sheeran_puett_phillips_dayton_2014, title={Ultrasound Imaging from Vaporization Signals Emitted by Phase Change Contrast Agents}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2014.0441}, abstractNote={Phase change contrast agents (PCCAs) exhibit a unique acoustic signature during the transition from a liquid droplet to a gas microbubble. Here, we demonstrate that this event can be used to generate an ultrasound image, and that the signal can be separated from that of a conventional microbubble. This presents a new opportunity to monitor PCCA activation in both diagnostic and therapeutic applications. A confocal, dual-frequency transducer was used to transmit 2 cycle, Gaussian enveloped sinusoids at 8 MHz and passively receive at 1 MHz. PCCAs were continuously infused through a microcellulose tube (250 μm diameter). At low pressures, vaporization signals from PCCAs were of significantly higher energy than signals emitted from the equivalent microbubble formulation. Specifically, when a peak negative pressure (PNP) of 0.51 MPa was transmitted, the contrast-to-noise ratio (CNR) was 18.94 dB for PCCAs and 2.28 dB for control microbubbles. As the PNP was increased to 0.76 MPa, these values changed to 22.1 dB and 9.73 dB, respectively. Time-domain averaging (TDA) helped to increase the separation of PCCA and microbubble signals. After TDA, the CNR at 0.76 MPa was 23.79 dB for PCCAs and 1.72 dB for microbubbles. The lateral resolution of the system was pressure dependent. With increasing pressure, the apparent diameter of the tube increased from 0.74 mm at 0.51 MPa to 1.14 mm at 0.76 MPa. This is due to the fact that the focal zone capable of activating PCCAs expands with increasing pressure.}, journal={2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Arena, Christopher B. and Novell, Anthony and Sheeran, Paul S. and Puett, Connor and Phillips, Linsey C. and Dayton, Paul A.}, year={2014}, pages={1778–1781} }